Novel Approach In Molecular Differentiation Of Prion Strains

August 30, 2008 — A team from the French Food
Safety Agency, Lyon, France, has identified a prion protein
characteristic that is unique to some natural but unusual sheep scrapie
cases. This finding may provide a novel method by which to study prion
diversity and their possible changes during cross-species transmission.

Mystery still surrounds the origin of the transmissible agent
involved in the food-borne epidemic of bovine spongiform encephalopathy
(BSE). Classical BSE, more commonly known as mad cow disease, is a
known cause of a variant form of the incurable, degenerative
neurological disorder Creutzfeldt-Jakob disease in humans. It has
recently been proposed that this could have been the result of the
recycling of an atypical, more probably sporadic form of BSE (called
bovine amyloidotic spongiform encephalopathy, or L-type BSE) in an
intermediate host, such as sheep.

The team, led by Thierry Baron, analyzed the molecular features of
the disease-associated protease-resistant prion protein (PrPres) to
determine any differences which might discriminate between scrapie and
BSE cases. The researchers sampled PrPres from the brains of transgenic
mice overexpressing the ovine prion protein after experimental
infection with prions from bovine classical BSE, L-type BSE, and ovine
scrapie. Scrapie cases were found to include rare ''CH1641-like''
isolates, which share some PrPres molecular features with classical BSE
and L-type BSE.

The molecular features of the prion protein in the "CH1641-like"
sheep scrapie cases more closely resemble those found in L-type BSE
compared to classical BSE. However, from a series of four "CH1641-like"
scrapie cases, the researchers found a pathological C-terminal prion
protein product that was undetectable from both L-type and classical
BSE transmitted to such mice, clearly suggesting that such scrapie
isolates are not linked to these BSE forms.

Further studies to confirm this discriminating factor are needed in
sheep, especially from sheep experimentally infected with L-type BSE,
which were not available for this study. These findings, however, add a
novel approach in the molecular differentiation of prion strains and
may help to better understand their possible changes during
cross-species transmissions.